1. Technical Background
The present invention relates to an antiinflammatory and analgesic transdermal gel containing a nonsteroidal antiinflammatory drug which is a propionic acid derivative as an effective ingredient. In particular, the present invention relates to a novel antiinflammatory and analgesic transdermal gel which is water-soluble and provides comparable antiinflammatory and analgesic activities to oral administered compositions while significantly reducing the systemic side effects and the gastrointestinal irritation associated with the oral administration of propionic acid derivatives.
2. The Prior Art
Typical examples of the nonsteroidal anti inflammatory propionic acid derivatives include ketoprofen, ibuprofen, flurbiprofen, naproxen, fenoprofen, benoxaprofen, indoprofen. pirprofen, carprofen, oxaprozin, pranoprofen, suprofen, alminoprofen, butibufen and fenbufen, etc. They have potent antiinflammatory and analgesic activities and are widely used for the treatment of rheumatic arthritis and its related conditions. Conventionally, these drugs have been administered orally in the form of solid preparations such as tablets and capsules. However, they have accompanied systemic side effects or gastrointestinal irritation following their oral administration. In order to reduce these side effects, these drugs have been formulated as transdermal preparations based on the fact that the skin permeability of these nonsteroidal antiinflammatory drugs are known to be relatively higher than other nonsteroidal antiinflammatory drugs. For examples, JP 58-39616, JP 58-83622, JP 58-103311, JP 61-238723 and U.S. Pat. Nos. 4,393,076 and 4,534,980 disclosed formulating nonsteroidal antiinflammatory drugs of propionic acid derivatives into transdermal preparations, generally an ointment or a cream. They claimed that the systemic side effects and gastrointestinal irritation of these drugs were significantly reduced while satisfied therapeutic effects were obtained. In these patents, they usually used carboxyvinyl polymer or hydroxypropylmethylcellulose as a gel base in the formulation of transdermal preparations of the drugs. However, the skin permeations of the drugs from their preparations were not enough to achieve pharmacological effects comparable to the oral administration of the drugs due to the low percutaneous absorption of the drugs from the preparations and, thus, a large amount of the preparation needed to be applied to achieve a desired efficacy.
As a result of extensive investigations with attempts to improve the shorcomings of the existing patents and products, the present inventors have succeeded in establishing a novel transdermal gel containing a nonsteroidal antiinflammatory drug which is a propionic acid derivative. The gel is water-soluble, has high skin permeation rate and, thus, excellent antiinflammatory and analgesic activities comparable to its oral administration. It, also, showed lowered systemic side effects and gastrointestinal irritation and good physicochemlcal stability.